肺炎衣原体Cpn0423通过Nod2/Rip2途径介导小鼠肺部炎症损伤及其作用机制研究

肺炎衣原体（Cpn）是一种重要的呼吸道病原体，新近发现Nod2参与Cpn感染的识别，但其作用机制不明。我们前期研究证实肺炎衣原体Cpn0423是一种定位于宿主细胞胞浆的分泌型蛋白，可诱导宿主细胞中Nod2活化及MIP-2等炎症因子分泌。据此，我们推测Cpn0423是Nod2的潜在配体，提出Cpn0423通过激活Nod2/Rip2路径介导小鼠肺部炎症损伤这一科学假说。本项目拟从细胞水平采用激光共聚集、荧光共振能量转移、信号通路阻断等手段，观察Nod2/Rip2途径对Cpn0423诱导宿主细胞产生炎症反应的影响；从动物水平上采用Nod2、Rip2基因敲除鼠模型，观察Nod2/Rip2途径对Cpn0423介导小鼠肺部炎症损伤的影响，最终阐明Cpn0423通过激活Nod2/Rip2路径及其介导小鼠肺部炎症损伤的作用机制，为拓展Cpn致病机制及肺炎衣原体感染性相关疾病的防治提供依据。

Chlamydia pneumoniae (C. pneumoniae) is an important respiratory pathogen. As reported recently, Nod2 receptor was involved in the recognition of C. pneumoniae infection and stimulation of innate immune response, however, whose mechanism is still unclearly. We have recently found that 1) C. pneumoniae Cpn0423 is a protein secreted from C. pneumoniae, which is located in the cytoplasm of host cell after C. pneumoniae infection and possess the ability to interact with the Nod2 receptor; 2) Cpn0423 could induce Nod2 overexpression and MIP-2 production in BMDM, suggesting Cpn0423 may be a potential ligand of Nod2 during Cpn infection. According to these previous findings, we hypothesize that Cpn0423 interacts with host Nod2 receptor, activates Nod2/Rip2 signal pathway, and induces pulmonary inflammation. To testify our hypothesis, lazer scan confocal microscope,fluorescence resonance energy transfer and signal pathway blocking will be used to analyze the effects of Nod2/Rip2 signal pathway on Cpn0423-induced immune response. Next, Nod2-/- and Rip2-/- animal models will be used to identify the the effects of Nod2/Rip2 signal pathway on Cpn0423-induced pulmonary inflammation. This study will not only provide theoretical and experimental evidence on further revealing the pathogenesis of Chlamydia pneumoniae, but also shed light on the prevention and clinical treatment on the disease related C. pneumonia infection.